1. Field of the Invention
The present invention relates to the field of molecular biology. The present invention discloses the discovery of the novel protein Isac. Isac has anticomplement activity and can be isolated and purified from the salivary glands of ticks or made by recombinant methods using various DNA expression techniques.
2. Description of the Related Art
The alternative pathway of complement is an evolutionarily old first line of defense against pathogens (Joiner, K. A. (1988) Ann. Rev. Microbiol. 42, 201–230). Complement activation leads to production of inflammatory anaphylatoxins (Hugli, T. E., and Muller-Eberhard, H. J. (1978) Adv. Immunol. 26, 1–53, Damerau, B. (1987) Rev. Physiol. Biochem. Pharmacol. 108, 152–206), and to the formation of a membrane attack complex leading to the lysis of the invading organism (Joiner, K. A. (1988) Ann. Rev. Microbiol. 42, 201–230). Endogenous regulators exist to prevent pathology associated with unconfined or inadvertent complement activation (Zipfel, P. F., Hellwage, J., Friese, M. A., Hegasy, G., Jokiranta, S. T., and Meri, S. (1999) Mol. Immunol. 36(4–5), 241–248, Kirschfink, M. (1997) Immunopharmacology 38(1–2), 51–62). Successful pathogens have developed several mechanisms to evade the host complement system (Joiner, K. A. (1988) Ann. Rev. Microbiol. 42, 201–230, Jokiranta, T. S., Jokipii, L., and Meri, S. (1995) Scand. J. Immunol. 42, 9–20, Wurzner, R. (1999) Mol. Immunol. 36(4–5), 249–260). In several of these evasion mechanisms, pathogens may recruit host complement regulatory molecules to their own surface or produce inhibitors of complement activation, which are either secreted or remain associated with their surfaces (Joiner, K. A. (1988) Ann. Rev. Microbiol. 42, 201–230, Jokiranta, T. S., Jokipii, L., and Meri, S. (1995) Scand. J. Immunol. 42, 9–20, Wurzner, R. (1999) Mol. Immunol. 36(4–5), 249–260, Rosengard, A. M., and Ahearn, J. M. (1999) Immunopharmacology 42(1–3), 99–106)
Ticks are ectoparasites that may feed for several days or even weeks with their mouthparts embedded into their vertebrate hosts. Although unnatural hosts can mount an effective immune response against ticks (Trager, W. (1939) J. Parasitol. 25, 57–81, Wikel, S. K. (1996) Ann. Rev. Entomol. 41, 1–22), only minor rejection reactions are observed when ticks feed on their natural hosts (Trager, W. (1939) J. Parasitol. 25, 57–81, Ribeiro, J. M. C. (1989) Exp. Appl. Acarol. 7, 15–20). The alternative pathway of complement was implicated in rejection reactions of guinea pigs against the tick Dermacentor andersoni (Wikel, S. K., and Allen, J. R. (1977) Immunology 32, 457–465, Wikel, S. K. (1979) Am. J. trop. Med. Hyg. 28, 586–590). The tick vector of Lyme disease in Eastern North America, Ixodes scapularis, can successfully feed repeatedly on its natural host, the white-footed mouse, Peromyscus leucopus (Trager, W. (1939) J. Parasitol. 25, 57–81, Davidar, P., Wilson, M., and Ribeiro, J. M. (1989) J. Parasitol. 75(6), 898–904), perhaps because it has salivary compounds that deactivate anaphylatoxins (Ribeiro, J. M. C., and Spielman, A. (1986) Exp. Parasitol. 62, 292–297) and inhibit the alternative pathway of complement (Ribeiro, J. M. C. (1987) Exp. Parasitol. 64, 347–353). Indeed, the host range of Ixodes correlates with their ability to counteract the alternative complement pathway of their most common hosts (Lawrie, C. H., Randolph, S. E., and Nuttall, P. A. (1999) Exp. Parasitol. 93(4), 207–214).